"This is a project to develop clinical reagents appropriate to administer in a prevention setting. Vitamin A analogues have more reported activity than any other class of agent used for the chemoprevention of tobacco-related malignancies. The relationship between the administered dose and the resulting effect in vivo is poorly understood. One of our publications reports the effects of serum proteins on the biological potency of retinoic acids. Albumin-retinoid interactions greatly decrease the effectiveness of 13 cis-retinoic acid in reducing the growth rate of lung cancer cells. This decrease in retinoid bioavailability is most likely a function of the common fatty acid structure shared by the major retinoids used to date for chemoprevention. We propose to change the route of administration of the retinoid to achieve higher local drug concentrations to overcome the retinoid neutralizing effect of serum albumin. The most important clinical lead from this work though is a fundamental reconsideration of the way in which drugs are administered for early, localized cancer."